NaSH increases SIRT1 activity and autophagy flux through sulfhydration to protect SH-SY5Y cells induced by MPP~

Parkinson's disease (PD) is one of the most prevailing aging diseases around the world. The present study was to investigate the potential effect of hydrogen sulfide (H₂S) and silent mating type information regulation 2 homolog 1 (SIRT1) in MPP~+ induced SH-SY5Y cells and its underlying mechanisms in PD. SH-SY5Y cells were induced by MPP~+ and treated with the H₂S donor NaHS to detect the effect of H₂S on the molecular behaviors of MPP~+ induced SH-SY5Y cells. NaHS reduced the Apoptosis rate and expressions of MDA, 4-HNE and p62, while increased cell viability, Autophagy flux and expressions of LC3 II/I and Beclin1 in MPP~+ induced SH-SY5Y cells. Then, levels of autophagy-related proteins and inflammation-related proteins (TNF-α, IL-Iβ) were detected, indicating that Chloroquine and Sirtinol reversed the protective effect of H₂S on SH-SY5Y cells induced by MPP~+. We further explored the particular function of H₂S, SH-SY5Y cells treated with MPP~+, NaHS chloroquine, and SIRT1 Inhibitor (Sirtinol). The results showed that H₂S increased SIRT1 expression and sulfhydration. Finally, a PD mouse model verified the above results. In a word, H₂S ameliorated SIRT1 activity through acceleration of SIRT1 sulfhydration to increase the Autophagy flux and attenuate damage of SH-SY5Y cells induced by MPP~+. H₂S and SIRT1 Activator might be a target in the treatment of PD patients.